This revised R21 grant is designed to foster collaborative research to study risk factors for cognitive decline among older adults living in the Indian state of Kerala. Our research sites are the cities of Kozhikode and Thiruvananthapuram in Kerala. The proposal will be directed by Dr Verghese, a neurologist at the Albert Einstein College of Medicine and a native of Kerala in collaboration with Dr. Mathuranath, Director, Division of Behavioral Neurology at the Sri Chitra Tirunal Institute, Thiruvananthapuram, one of India's premier postgraduate medical institutes and Dr Salam, Director of Neurology at Baby Memorial Hospital, Kozhikode. We have entitled this collaboration, 'The Kerala-Einstein Study'. Our overall goals are: 1) develop sustained collaborations between US and Kerala researchers;2) create a research network in Kerala building on existing research and clincial facilities;and 3) Show feasibility and generate preliminary data for future joint proposals to address age related cognitive and motor outcomes. Research capacity building activities include developing uniform diagnostic procedures, developing and validating culture fair instruments such as a picture-based memory impairment screen (Study 1), supporting research training, creating computerized databases, and exploring the feasibility of establishing brain banking. The prevalence of dementia in Kerala seniors is 1.3 to 5.3%. An increasing prevalence of cardiovascular disease has also been reported in Kerala. Cardiovascular risk factors, cerebrovascular disease, and dementia often coexist, but it is unclear if the relation between these problems is coincidental or causal. We propose to examine the role of cardiovascular disease as well as other risk factors (gait abnormalities, low education, and leisure activities) for dementia in Kerala seniors. Over the 2-year study period, we will examine these variables in a case control study in a clinic-based sample of 400 adults in Kozhikode (Study 2) as well as longitudinally in over 2000 older adults participating in an ongoing cohort study in Thiruvananthapuram (Study 3). The Kerala-Einstein study has the potential to have a major impact on future research and clinical practice in Kerala and USA, and will build the foundation for future long term studies of risk factors for age related cogitive and motor decline utilizing collaborative arrangements developed through this proposal. PUBLIC HEALTH RELEVANCE: This R21 grant is designed to foster collaborative research between US and Indian investigators to study risk factors, especially cardiovascualr diseases, for cognitive decline among older adults living in the Indian state of Kerala. Our research sites are in the cities of Kozhikode and Thiruvananthapuram in Kerala. We also propose to develop research infrastructure and train junior faculty to sustain future research efforts.